Abstract
Background: In peritoneal dialysis (PD), residual renal function (RRF) fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE) contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE-mediated toxicity by blocking hyperglycemia-associated podocyte damage via the pentose-phosphate pathway.Methods: A human differentiated podocyte cell line was incubated with control solution (control), 2.5% glucose solution (glucose), and 2.5% peritoneal dialysis fluid (PDF) for 48 h either ±50 μM benfotiamine. Podocyte damage and potential benefit of benfotiamine were analyzed using immunofluorescence, western blot analysis, and a functional migration assay. For quantitation, a semiquantitative score was used.Results: When incubating podocytes with benfotiamine, glucose, and PDF-mediated damage was reduced, resulting in lower expression of AGE and intact podocin and ZO-1 localization. The reorganization of the actin cytoskeleton was restored in the presence of benfotiamine as functional podocyte motility reached control level. Decreased level of inflammation could be shown as well as reduced podocyte apoptosis.Conclusion: These data suggest that benfotiamine protects podocytes from glucose and PDF-mediated dysfunction and damage, in particular, with regard to cytoskeletal reorganization, motility, inflammation, and podocyte survival.
Highlights
Preservation of residual renal function (RRF) contributes significantly to an improved survival of patients undergoing peritoneal dialysis (PD) [1,2,3]
Short summary: It is known that high glucose and advanced glycation end-products (AGE) do cause local peritoneal toxicity and systemic damage and thereby cause a loss of residual renal function (RRF)
When treating podocytes with the vitamin B1 analog benfotiamine, damage mediated by high glucose and peritoneal dialysis (PD) fluids is reduced, in particular, regarding cytoskeletal organization, motility, inflammation, as well as podocyte survival; this might be an implication for preservation of RRF in PD
Summary
Preservation of residual renal function (RRF) contributes significantly to an improved survival of patients undergoing peritoneal dialysis (PD) [1,2,3]. As a consequence of reabsorption, the effects of the PDFs are not limited to the peritoneal cavity, and studies have shown that the kidneys are susceptible, leading to damage, and decreased RRF [7,8,9,10,11]. Glucose degradation products are a heterogeneous group of small molecular weight carbonyls formed within PDFs as a direct consequence of heat-sterilization [12]. They exhibit a facile reactivity with various biomolecules, including proteins, DNA, and phospholipids, generating stable products, such as advanced glycation end-products (AGEs). Benfotiamine could counteract the glucose and AGE-mediated toxicity by blocking hyperglycemia-associated podocyte damage via the pentose-phosphate pathway
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